37: Voluntary Movement: The Primary Motor Cortex

• Motor Functions Are Localized within the Cerebral Cortex

• Many Cortical Areas Contribute to the Control of Voluntary Movements

  • Voluntary Motor Control Appears to Require Serial Processing

  • The Functional Anatomy of Precentral Motor Areas is Complex

  • The Anatomical Connections of the Precentral Motor Areas Do Not Validate a Strictly Serial Organization

• The Primary Motor Cortex Plays an Important Role in the Generation of Motor Commands

  • Motor Commands Are Population Codes

  • The Motor Cortex Encodes Both the Kinematics and Kinetics of Movement

  • Hand and Finger Movements Are Directly Controlled by the Motor Cortex

  • Sensory Inputs from Somatic Mechanoreceptors Have Feedback, Feed-Forward, and Adaptive Learning Roles

  • The Motor Map Is Dynamic and Adaptable

  • The Motor Cortex Contributes to Motor Skill Learning

• An Overall View

One of the main functions of the brain is to direct the body's purposeful interaction with the environment. Understanding how the brain fulfils this role is one of the great challenges in neural science. Because large areas of the cerebral cortex are implicated in voluntary motor control, the study of the cortical control of voluntary movement provides important insights into the functional organization of the cerebral cortex as a whole.

Evolution has endowed mammals with adaptive neural circuitry that allows them to interact in sophisticated ways with the complex environments in which they live. Adaptive patterning of voluntary movements gives mammals a distinct advantage in locating food, finding mates, and avoiding predators, all of which enhance the survival potential of the individual and a species.

The ability to use fingers, hands, and arms in voluntary actions independent of locomotion further helps primates, and especially humans, exploit their environment. Most animals must search their environment for food when hungry. In contrast, humans can also "forage" by using their hands to cook a meal or simply punch a few buttons on a telephone and order takeout. The central neural circuits responsible for such nonlocomotor behavior emerged from and remain intimately associated with the phylogenetically older circuits that control the forelimb during locomotor behaviors.

In this and the following chapter we focus on the control of voluntary movements of the hand and arm in primates. In this chapter we describe the cortical networks that control voluntary movement, particularly the role of the primary motor cortex in the generation of motor commands. In the next chapter we address broader questions about cortical control of voluntary motor behavior, in particular how the cerebral cortex organizes the stream of incoming sensory information to guide voluntary movement.

Voluntary movements differ from reflexes and basic locomotor rhythms in several important ways. By definition they are intentional—they are initiated by an internal decision to act—whereas reflexes are automatically triggered by external stimuli. Even when a voluntary action is directed toward an object, such as reaching for a cup, the cause of action is not the object but an internal decision to interact with the object. The presence of the object provides only the opportunity for acting. Voluntary actions involve choices between alternatives, including the choice not to act. Furthermore, they are organized to achieve some goal in the near or distant future.

Voluntary movements often have a labile, context-dependent association with sensory inputs. The same object can evoke different voluntary actions or no response at all depending on the context in which it appears. That is, the neural circuits controlling voluntary behavior are able to differentiate between an object's physical properties and its behavioral salience.

The nature and effectiveness of voluntary movements often improve with experience. The motor system can learn new behavioral strategies or new reactions to familiar stimuli to improve behavioral outcomes, and it can learn new skills to cope with predictable variations and perturbations of the environment.

Thus the neural control of voluntary movement involves far more than simply generating a particular pattern of muscle activity. It also involves processes that are usually considered to be more sensory, perceptual, and cognitive in nature. As we shall see, these processes are not rigidly compartmentalized into different neural structures or neural populations.

For centuries it was believed that the human cerebral cortex was responsible for only higher-order, conscious mental functions. In the middle of the 19th century the English neurologist John Hughlings Jackson made the controversial proposal that a specific part of the cerebral cortex anterior to the central sulcus has a causal role in movement. He reached this conclusion from treating patients with epileptic seizures that were characterized by repeated spasmodic involuntary movements that sometimes resembled fragments of purposive voluntary actions.

During each episode the seizures always spread to different body parts in a fixed temporal sequence that varied from patient to patient, a pattern called Jacksonian march. Jackson concluded that paroxysmal neural activity generated by epileptic foci located near the central sulcus caused the involuntary seizures. He speculated that the progression of seizures across the body resulted from the spread of paroxysmal activity across small clusters of neurons lying along the central sulcus, each of which controlled movement of a different body part. Jackson's proposal that a discrete cortical region is involved in the control of movement was a strong argument for the localization of different functions in distinct parts of the cerebral cortex. His observations, along with contemporaneous studies by Pierre Paul Broca and Karl Wernicke on the language deficits resulting from specific cortical lesions, laid the foundation for the modern scientific study of cortical function.

It was not until later in the 19th century, however, when improved anesthesia and aseptic surgical techniques allowed direct experimental study of the cerebral cortex in live subjects, that conclusive experimental evidence for a discrete region of the cerebral cortex devoted to motor function was possible. Gustav Fritsch and Eduard Hitzig in Berlin and David Ferrier in England showed that electrical stimulation of the surface of a limited area of cortex of different surgically anesthetized mammals evoked movements of parts of the contralateral body. The electric currents needed to evoke movements were lowest in a narrow strip along the rostral bank of the central sulcus.

Their experiments demonstrated that, even within this strip of tissue, discrete sites contained neurons with distinctive functions. Stimulation of adjacent sites evoked movements in adjacent body parts, starting with the foot, leg, and tail medially, and proceeding to the trunk, arm, hand, face, mouth, and tongue more laterally. When they lesioned a cortical site at which stimulation had evoked movements of a part of the body, motor control of that body part was perturbed or lost after the animal recovered from surgery. These early experiments showed that the motor strip contains an orderly motor map of the contralateral body and that the integrity of the motor map is necessary for voluntary control of the corresponding body parts.

In the first half of the 20th century more focal electrical stimulation allowed the motor map to be defined in greater detail. Clinton Woolsey and his colleagues tested the functional organization of the motor cortex in several species of mammals, whereas Wilder Penfield and co-workers tested discrete sites in human neurosurgical patients (Figure 37–1). Their findings demonstrated that the same general topographic organization is conserved across many species. One important discovery was that the motor map is not a point-to-point representation of the body. Instead, the most finely controlled body parts, such as the fingers, face, and mouth, are represented in the motor map by disproportionately large areas, reflecting the larger number of neurons needed for fine motor control.

Woolsey and Penfield both recognized, however, that their simple motor map masked a deeper complexity. Today the best-studied regions of the map are those parts controlling the arm and hand. Recent mapping studies have revealed that the neurons controlling the muscles of the digits, hand, and distal arm tend to be concentrated within a central zone, whereas those controlling more proximal arm muscles are located in a horseshoe-shaped ring around the central core (Figure 37–2A). Furthermore, across the concentrically organized areas of the arm motor map there is extensive overlap of stimulation sites that causes contractions of muscles acting across different joints; conversely, each muscle can be activated by stimulating many widely dispersed sites (Figure 37–2B). Moreover, different combinations of muscle contractions and joint motions can be evoked by stimulating different sites. Finally, local horizontal axonal connections link different sites, allowing neural activity at multiple output sites in the map to be coordinated during the formation of motor commands.

To date, studies have not revealed any repeating functional elements in the fine details of the motor map for the arm and hand analogous to the ocular- dominance bands and orientation pinwheels in the visual cortex. However, the complex, extensively overlapped organization of the arm motor map and the network of local horizontal connections likely provide a mechanism to coordinate whole-limb actions such as reaching to grasp and manipulate an object.

Voluntary Motor Control Appears to Require Serial Processing

Much of what we do in everyday life involves a sequence of actions. One normally does not take a shower after getting dressed or put cake ingredients into the oven to bake before blending them into a batter. It seems logical that most brain functions are also serial.

Largely on the basis of indirect psychological studies, the neural processes by which the brain controls voluntary behavior are commonly divided into three sequential stages. First, perceptual mechanisms generate a unified sensory representation of the external world and the individual within it. Next, cognitive processes use this internal replica of the world to decide on a course of action. Finally, the selected motor plan is relayed to action systems for implementation (Figure 37–3A).

The final stage, execution of the chosen motor plan, also appears to be serial in nature. It has often been modeled as a series of sensorimotor transformations of representations of a movement into different coordinate frameworks, progressing from a general description of the overall form of the movement to increasingly specific details, culminating in patterns of muscle activity (Figure 37–3B).

According to this serial scheme, each sequential operation is encoded by a different neuronal population. Each population encodes specific features or parameters of the intended movement in a particular coordinate system, such as the direction of movement of the hand through space or the patterns of muscle contractions and forces. These several populations are connected serially and only the last population in the chain projects to the spinal cord.

As we shall see in this and the next chapter, this model has some heuristic value for describing how the brain is organized to control voluntary movement, but direct neurophysiological studies of neural mechanisms show that a strict adherence to serial processing is simplistic and incorrect. We know now for instance that the brain does not have a single, unified perceptual representation of the world (see Chapter 38). The serial scheme also wrongly implies that the only role of the motor system is to determine which muscles to contract, when, and by how much. We now know that several cortical motor areas also play a critical role in the actual choice of what action to take, a process that is usually considered more "cognitive" than "motor." This is described in more detail in Chapter 38.

The Functional Anatomy of Precentral Motor Areas is Complex

In the early 20th century Alfred Campbell and Korbinian Brodmann divided the human cerebral cortex into a large number of cytoarchitectonic areas with distinct anatomical features. They noted that the precentral cortex in the gyri immediately rostral to the central sulcus lacks the six layers characteristic of most cerebral cortex. It lacks a distinct internal granule cell layer and thus is often called agranular cortex. Campbell and Brodmann subdivided the precentral cortex into caudal and rostral parts, which Brodmann designated cytoarchitectonic areas 4 and 6 (Figure 37–4).

Campbell proposed that these two regions were functionally distinct motor areas. He thought that the caudal region, or primary motor cortex, controlled the motor apparatus in the spinal cord and generated simple movements. The rostral region, he argued, was specialized for higher-order aspects of motor control and for movements that are more complex, conditional, and voluntary in nature. He thought that these areas influenced movement indirectly by projecting to the primary motor cortex and so he named them the premotor cortex.

Some years later, while mapping motor areas of cortex with electrical stimuli, Clinton Woolsey and his colleagues discovered that movements of the contralateral body can be evoked not only by electrical stimulation of the primary motor cortex, but also by stimulating a second region in a part of the premotor cortex on the medial surface of the cerebral hemisphere now known as the supplementary motor area (Figure 37–4B). The motor map of different body parts evoked by stimulation of the supplementary motor area is less detailed than that of the primary motor cortex and lacks the enlarged distal arm and hand representation seen in the primary motor cortex. Stimulation of the supplementary motor area can evoke movements on both sides of the body or halt ongoing voluntary movements, effects that rarely result from stimulation of the primary motor cortex.

Anatomical and functional studies in humans and nonhuman primates over the past 25 years have radically changed the view of how the precentral cortex is organized functionally. First, architectonic studies demonstrated that Brodmann's area 6 is not homogeneous but consists of several distinct subareas. Second, these subareas have specific connections among themselves and with the rest of the cerebral cortex. Third, functional studies found that each subarea separately controls movements of some or all parts of the body and that the properties of neurons in each subarea differ in important ways. These areas are identified by two different nomenclatures in the literature.

As a result, in current maps of the precentral cortex Brodmann's area 6 is usually divided into five or six functional areas in addition to the primary motor cortex (or area F1) in Brodmann's area 4 (Figure 37–4B). The classical supplementary motor area originally identified by Woolsey on the medial cortical surface is now split into two functional regions. The more caudal part is called the supplementary motor area proper (area F3), whereas the more rostral part is the pre-supplementary motor area (F6). The caudal and rostral parts of the dorsal convexity of area 6 are called the dorsal premotor cortex (F2) and pre-dorsal premotor cortex (F7), respectively. The ventral convexity of Brodmann's area 6 has also been identified as a separate functional area called the ventral premotor cortex, and has been further subdivided into two subareas called F4 and F5 (Figure 37–4B). Finally, three additional motor areas outside Brodmann's area 6, in the rostral cingulate cortex, have been delineated recently.

The multiplicity of cortical motor areas would seem redundant if their only role was to initiate or coordinate muscle activity. However, we now know that neurons in these areas have unique properties and interact to perform diverse operations that select, plan, and generate actions appropriate to external and internal needs and context.

The Anatomical Connections of the Precentral Motor Areas Do Not Validate a Strictly Serial Organization

To understand the roles of these multiple precentral motor areas in voluntary motor control, it is important to know their connections with one another, their connections with other cortical areas, and their descending projections.

The cortical motor areas are interconnected by complex patterns of reciprocal, convergent, and divergent projections rather than simple serial pathways. The supplementary motor area, dorsal premotor cortex, and ventral premotor cortex have somatotopically organized reciprocal connections not only with the primary motor cortex but also with each other. The primary motor cortex and supplementary motor area receive somatotopically organized input from the primary somatosensory cortex and the rostral parietal cortex, whereas the dorsal and ventral premotor areas are reciprocally connected with progressively more caudal, medial, and lateral parts of the parietal cortex. These somatosensory and parietal inputs provide the primary motor cortex and caudal premotor regions with sensory information to organize and guide motor acts.

In contrast, the pre-supplementary and pre-dorsal premotor areas do not project to the primary motor cortex and are only weakly connected with the parietal lobe. They receive higher-order cognitive information through reciprocal connections with the prefrontal cortex and so may impose more arbitrary context-dependent control over voluntary behavior.

Several cortical motor regions project in multiple parallel tracts to subcortical areas of the brain as well as the spinal cord. The best studied output path is the pyramidal tract, which originates in cortical layer V in a number of precentral and parietal cortical areas. Precentral areas include not only primary motor cortex but also the supplementary motor and dorsal and ventral premotor areas. The pre-supplementary motor and pre-dorsal premotor areas do not send axons to the spinal cord; their descending output reaches the spinal cord indirectly through projections to other subcortical structures. Parietal areas that contribute descending axons to the pyramidal tract include the primary somatosensory cortex and adjacent rostral parts of the superior and inferior parietal lobules.

Many pyramidal tract axons decussate at the pyramid and project to the spinal cord itself, forming the corticospinal tract (Figure 37–5A). Because several cortical areas contribute axons to the corticospinal tract, the traditional view that the primary motor cortex is the "final common path" from the cerebral cortex to the spinal cord is incorrect. Instead, several premotor and parietal areas of cortex can also influence spinal motor function through their own corticospinal projections.

Many corticospinal axons from the primary motor cortex and premotor areas in primates, and virtually all corticospinal axons in other mammals, terminate on spinal interneurons in the intermediate region of the spinal cord (Figure 37–5B). These interneurons are components of reflex and pattern-generating circuits that produce stereotypical motor synergies and locomotor rhythms (see Chapter 36). In primates much of the control exerted by the primary motor cortex on spinal motor circuits and all of the control from premotor areas is mediated indirectly through these descending cortical projections to spinal interneurons.

In primates the terminals of some corticospinal axons also extend into the ventral horn of the spinal cord (lamina IX) where they arborize and contact the dendrites of spinal motor neurons (Figure 37–6B; Figure 37–5B). These monosynaptically projecting cortical neurons are called corticomotoneurons. The axons of these neurons become a progressively larger component of the corticospinal tract in primate phylogeny from prosimians to monkeys, great apes, and humans.

In monkeys corticomotoneurons are found only in the most caudal part of the primary motor cortex that lies within the anterior bank of the central sulcus. There is extensive overlap in the distribution of the corticomotoneurons that project to the spinal motor neuron pools innervating different muscles (Figure 37–6A). In monkeys more corticomotoneurons project to the motor neuron pools for muscles of the digits, hand, and wrist than to those for more proximal parts of the arm.

The terminal of a single corticomotoneuron axon often branches and terminates on spinal motor neurons for several different agonist muscles, and can also influence the contractile activity of still more muscles through synapses on spinal interneurons (Figure 37–6B, C). This termination pattern is functionally organized to produce coordinated patterns of activity in a muscle field of agonist and antagonist muscles. Most frequently, a single corticomotoneuron axon directly excites the spinal motor neurons for several agonist muscles and indirectly suppresses the activity of some antagonist muscles through local inhibitory interneurons (Figure 37–6C). The fact that corticomotoneurons are more prominent in humans than in monkeys may be one of the reasons why lesions of the primary motor cortex have such a devastating effect on motor control in humans compared to lower mammals (Box 37–1).

Although neurons in several motor-cortical areas send axons into the corticospinal tract, the primary motor cortex has the most direct access to spinal motor neurons, including the monosynaptic projections of corticomotoneurons. However, the corticospinal tract is not the only pathway for descending control signals to spinal motor circuits. The spinal cord also receives inputs from the rubrospinal, reticulospinal, and vestibulospinal tracts. These pathways influence movement through monosynaptic terminations onto spinal interneurons and spinal motor neurons.

In summary, a strictly serial organization of voluntary movement would require a pattern of serial connections between cortical areas, ending at the primary motor cortex, which then projects to the spinal cord. In reality, however, the multiple precentral and parietal cortical motor areas are interconnected by a complex network of reciprocal, divergent, and convergent axonal projections. Moreover, several cortical areas project to the spinal cord in parallel with projections from the primary motor cortex. Finally, the spinal motor circuits receive inputs from several subcortical motor centers in addition to those from the cerebral cortex.

In the 1950s Herbert Jasper and colleagues pioneered chronic microelectrode recordings from alert animals engaged in natural behaviors. This approach, which allows researchers to study the activity of single neurons while animals perform a controlled behavioral task, has made enormous contributions to our knowledge of the neuronal mechanisms underlying many brain functions. A microelectrode can also be used to deliver weak electrical currents to a small volume of tissue around its tip. When used in the cerebral cortex, this technique is called intracortical microstimulation.

These methods have been complemented more recently by techniques that can be used in human subjects, such as functional imaging and transcranial magnetic stimulation. Nearly every insight that will be described in the rest of this chapter and in Chapter 38 has been derived from these techniques.

Edward Evarts, the first to use chronic microelectrode recordings to study the primary motor cortex in behaving monkeys, made several discoveries of fundamental importance. He found that single neurons in this area discharge during movements of a limited part of the contralateral body, such as one or two adjacent joints in the hand, arm, or leg (Figure 37–9). Some neurons discharge during flexion of a particular joint and are reciprocally suppressed during extension, whereas other cells display the opposite pattern. This movement-related activity typically begins 50 to 150 ms before the onset of agonist muscle activity. These pioneering studies suggested that single neurons in primary motor cortex generate signals that provide specific information about movements of specific parts of the body before those movements are executed.

Many subsequent studies have provided further insight into the contribution of different cortical motor areas to the control of voluntary movements. In general, the output signals from premotor areas are strongly dependent on the context in which the action is performed, such as the stimulus-response associations and the rules that guide which movement to make. In contrast, the commands generated by the primary motor cortex are more closely related to the mechanical details of the movement and are usually less influenced by the behavioral context. However, the relative role of these different areas to voluntary motor control, including the primary motor cortex itself, continues to be an area of active research and controversy. The rest of this chapter and Chapter 38 describe our current understanding of the different roles of cortical motor areas.

Columnar arrays of neurons with similar response properties are a prominent feature of many sensory areas of cortex. It is surprising therefore that there is only weak evidence for such functional columns in the primary motor cortex. The cell bodies and apical dendrites of primary motor cortex neurons tend to form radially oriented columns. The terminal arbors of thalamocortical and corticocortical axons form localized columns or bands and corticomotoneurons tend to cluster in small groups with similar muscle fields. Motor cortex neurons recorded successively as a microelectrode descends perpendicularly through the neuronal layers between the pial surface and the white matter typically discharge during movements of the same part of body and can have similar preferred movement directions. Nevertheless, adjacent cells often show very different response patterns.

Motor Commands Are Population Codes

The complex overlapping organization of the motor map for the arm and hand suggests at least two different ways to generate the motor command for a given movement. The map could function as a look-up table within which a desired movement is generated by selective activation of a few sites whose combined output produces all the required muscle activity and joint motions. Or it could be a distributed functional map in which many sites contribute to each motor command.

Apostolos Georgopoulos and colleagues recorded from the primary motor cortex while a monkey reached in different directions from a central starting position toward targets arrayed on a circle in the horizontal plane. Individual neurons responded during many movements, not just a single one (Figure 37–10A). Each neuron's activity was strongest for a preferred direction and often weakest for the opposite direction, as Evarts had found for single-joint movements. However, each cell also responded in a graded fashion to directions of movement between the preferred and the opposite directions. Its activity pattern thus formed a broad directional tuning curve, maximal at the preferred direction and decreasing gradually with increasing difference between the preferred direction and the target direction.

Different cells had different preferred directions, and their tuning curves overlapped extensively. All directions were represented in the neuronal population. Cells with similar preferred directions were located at several different sites in the arm motor map, and nearby cells often had different preferred directions. As a result, many cells with a broad range of preferred directions discharged at different intensities at many locations across the arm motor map during each reaching movement.

Despite the apparent complexity of the response properties of single neurons, Georgopoulos found that the global pattern of activity of the entire population provided a clear signal for each movement. He represented each cell's activity by a vector pointing in the cell's preferred direction. The vector's length for each direction of movement was proportional to the mean level of activity of that cell averaged over the duration of the movement (Figure 37–10B). This vectorial representation implied that an increase of activity of a given cell is a signal that the arm should move in the cell's preferred direction, and that the strength of this directional influence varies continuously for different reach directions as a function of the neuron's directional tuning.

Vectorial addition of all of the single-cell contributions to each output command produces a population vector that corresponds closely to the actual movement direction. That is, an unambiguous signal about the desired motor output is encoded by the summed activity of a large population of active neurons throughout the arm motor map in the primary motor cortex. As a result, neurons in all parts of the arm motor map contribute to the motor command for each reaching movement, and the pattern of activity across the motor map changes continuously as a function of the intended direction of the reaching movement.

Andrew Schwartz and colleagues used the same population-vector analysis to represent temporal variations in the activity of populations of primary motor cortex neurons every 25 ms while monkeys performed continuous arm movements. In the resulting time sequence of population vectors, each vector predicts the instantaneous direction and speed of the motion of the monkey's arm approximately 100 ms later (Figure 37–11). These results show that the pattern of neural activity distributed across the arm motor map varies continuously in time during complex arm movements, signaling the moment-to-moment details of the desired movement.

Further studies have confirmed that similar population-coding mechanisms are used in all cortical motor areas. This common coding mechanism undoubtedly facilitates the communication of movement-related information between the multiple areas of motor cortex during voluntary behavior.

The Motor Cortex Encodes Both the Kinematics and Kinetics of Movement

Population-vector analyses show that neural activity in the primary motor cortex contains information about the trajectory of hand motions during reaching and drawing movements. However, to execute those movements the motor system must implement the desired motions by generating particular patterns of muscle activity.

Electrical stimulation of the primary motor cortex readily evokes muscle contractions, and some cells in this region have direct access to spinal motor neurons. Indeed, it was long assumed that the major role of the primary motor cortex was to specify the muscle activity that generates voluntary movements. Because muscle contractions generate the forces that displace a joint or limb in a particular direction, a critical question is whether primary motor cortex neurons signal the desired spatiotemporal form of a behavior or the forces and muscle activity required to generate the movement. That is, do these neurons encode the kinematics or the kinetics of an intended movement (Box 37–2)?

Kinematics refers to the parameters that describe the spatiotemporal form of movement, such as direction, amplitude, speed, and path. Kinetics concerns the causal forces and muscle activity. It is also useful to distinguish the dynamic forces that cause movements from the static forces required to maintain a given posture against constant external forces such as gravity.

Evarts was the first to address this question with single-neuron recordings. Using a system of pulleys and weights, he applied a load to the wrist of a monkey to pull the wrist in the direction of flexion or extension. To make a particular movement the animal had to alter its level of muscle activity to compensate for the load. As a result, the kinematics (direction and amplitude) of wrist movements remained constant but the kinetics (forces and muscle activity) changed with the load. The activity of many primary motor cortex neurons associated with movements of the hand and wrist increased during movements in their preferred direction when the load opposed that movement but decreased when the load assisted it (Figure 37–12). These changes in neural activity paralleled the changes in muscle activity required to compensate for the external loads. This was the first study to show that the activity of many primary motor cortex neurons is more closely related to how a movement is performed, the kinetics of motion, than to what movement is performed, the corresponding kinematics.

A later study confirmed this property of motor cortex activity during whole-arm reaching movements. A monkey made arm movements exactly as in the task used by Georgopoulos (Figure 37–10), but additional external loads pulled the arm in different directions. To continue to move the arm along the same path, the monkey had to change the activity of its arm muscles to counteract the external loads. The level of activity of many motor cortex neurons changed systematically with the direction of the external load even though the movement path did not change. When the load opposed the direction of reach, the single-cell and total population activity increased. When the load assisted the reaching direction, the neural activity decreased in a manner that signaled the change in muscle activity and output forces required to make the movement (Figure 37–13).

Other studies have examined the issue whether the primary motor cortex organizes the kinematics or kinetics of movement by using tasks in which subjects generate isometric forces against immovable objects rather than moving the arm. The activity of many primary motor cortex neurons varies with the direction and level of static isometric output forces generated across a single joint, such as the wrist or elbow, as well as during precise pinches with the thumb and index finger (Figure 37–14A). At least over part of the tested range these responses vary linearly with the level of static force. When a monkey uses its whole arm to exert isometric force in different directions, the activity of many motor cortex neurons varies systematically with force direction, and the directional tuning curves resemble those for activity associated with reaching movements (Figure 37–14B). Because no movement is intended or produced in isometric tasks, this strongly suggests that the primary motor cortex contributes to the control of static and dynamic output forces during many motor actions.

Finally, several studies have found that the activity of some motor cortex neurons can be correlated with the detailed contraction patterns of specific muscles during such diverse tasks as isometric force generation, precision pinching of objects between the thumb and index finger, and complex reaching and grasping actions (Figure 37–15).

These findings show that some neurons in the primary motor cortex can provide information about the causal forces and muscle activity of motor outputs. Nevertheless, the activity of other neurons in the primary motor cortex appears to signal the desired kinematics of arm and hand movements rather than their kinetics, or the desired direction of isometric force but not its magnitude. Perhaps most surprisingly, the activity of some corticomotoneurons does not always correlate with the contraction of their target muscles. For instance, some corticomotoneurons discharge strongly while a monkey generates weak contractions of the target muscles to make carefully controlled delicate movements of the hand and fingers, but are nearly silent when the monkey generates powerful contractions of the same muscles to make brisk, forceful movements.

How can we reconcile these apparently contradictory findings about the role of the primary motor cortex in the control of movement? According to the serial model of motor control all of the neurons in the primary motor cortex should have similar properties and so should represent either the kinematics or kinetics of the desired movement, but not both. However, the experimental evidence suggests that a strictly serial model is too simplistic. The response properties of primary motor cortex neurons are not homogeneous. Signals about both the desired kinematics and required kinetics of movements may be generated simultaneously in different, or possibly even overlapping, populations of primary motor cortex neurons. Rather than representing only what movement to make (kinematics) or how to make it (kinetics), the true role of the motor cortex may be to perform the transformation between these two representations of voluntary movements.

Delineating the movement-related information encoded in motor cortex activity is increasingly important for the development of brain-controlled interfaces and neuroprosthetic controllers that allow patients with severe motor deficits to control remote devices such as a computer cursor, a wheelchair, or a robotic limb by neural activity alone (Box 37–3).

Hand and Finger Movements Are Directly Controlled by the Motor Cortex

The monosynaptic projection from the primary motor cortex onto spinal motor neurons is most dense for muscles of the distal arm, hand, and fingers. This arrangement allows the primary motor cortex to regulate the activity of those muscles directly, in contrast to its indirect regulation of muscles through the reflex and pattern-generating functions of the spinal circuits. It also provides primates and humans with a greatly enhanced capacity for individuated control of hand and finger movements. Large lesions of the primary motor cortex permanently destroy this capacity.

Although monkeys and humans can make isolated movements of the thumb and fingers, most hand and finger actions involve combinations of stereotypical hand and finger configurations and coordinated wrist and digit movements. This has led to the hypothesis that separate cortical circuits selectively control these different stereotypical hand actions, and that the primary motor cortex converts these signals into more specific motor commands (see Chapter 38).

The anatomy of the muscles of the wrist and fingers further complicates the commands for individuated finger and hand movements. Several muscles have long, bifurcating tendons that act across several joints and even act on several fingers rather than just one. As a consequence, individuated control of hand and finger movements requires highly specific patterns of activation and inhibition of multiple muscles.

Cortical neurons controlling the hand and digits occupy the large central core of the primary motor cortex motor map but also overlap extensively with populations of neurons controlling more proximal parts of the arm (see Figure 37–2A). Some neurons within the central core discharge preferentially during movements of a single digit, but many discharge during coordinated movements of several digits, and even of the wrist and more proximal joints. Neurons that discharge during movements of different digits are distributed throughout the motor map in an extensively overlapping fashion. As a result, neural activity required to generate an individuated action of the hand and digits is distributed broadly across the distal arm and hand areas of the motor map, as is also the case for the output to more proximal parts of the arm.

This highly intermixed organization of the hand and digit motor map stands in striking contrast to the much more highly ordered representation of tactile sensory inputs from different parts of the hand and digits in the primary somatosensory cortex. This difference likely reflects differences in the cortical mechanisms required to analyze the spatiotemporal distribution of tactile input on the hand and digits versus those needed to coordinate individuated movements of the digits and hand.

Sensory Inputs from Somatic Mechanoreceptors Have Feedback, Feed-Forward, and Adaptive Learning Roles

Many primary motor cortex neurons receive sensory input from proprioceptors or cutaneous mechanoreceptors. The tactile input is particularly prominent on neurons implicated in the control of hand and digit movements. These inputs inform the motor system about the current state of the body, such as the position, posture, and movement of the arm and hand and their interactions with the environment. This information can play at least three functional roles: in feedback control of ongoing movements, in feed-forward control of intended movements, and as a teaching signal during motor learning.

Sensory feedback from the arm provides information about both the progress of an ongoing arm movement and deviations from the intended path that should be corrected. Feedback corrections during movement are implemented by neural circuits at many levels of the motor system, ranging from reflex responses in the spinal cord to corrective adjustments of voluntary motor commands from the motor cortex. Similarly, the activity of many neurons in the primary motor cortex that control hand movements is strongly influenced by tactile stimuli on the glabrous surface of the digits and palm of the hand. This tactile input helps adjust the output signal from hand-related neurons to ensure that the subject applies enough force to the surface of an object to grasp and manipulate it, but not to crush it or let it slip.

Sensory feed-forward control involves continuously adjusting the level and distribution of neuronal activity throughout the cortical motor map to reflect the limb's current state of posture and movement. By pretuning the pattern of activity in the motor-cortical map and spinal motor apparatus as a function of the limb's motor state before the onset of a movement, somatic sensory input helps to assure that the appropriate motor command is generated in the motor cortex and converted into the appropriate patterns of muscle activity at the spinal level.

Finally, sensory input can provide information about errors experienced during movement that could be used by adaptive motor circuits to make changes to future motor commands, thus facilitating motor learning.

The Motor Map Is Dynamic and Adaptable

The mediolateral sequence of major body segments in the motor map is highly consistent across individuals, but the details in each functional subregion can vary. This suggests that the motor map is continually shaped by an individual's motor experience. The dynamic nature of the map has been demonstrated in several ways. For instance, functional reorganization often occurs after a focal lesion so that some of the movements that had been evoked by the injured tissue are now generated by the adjacent cortex. This reorganization likely contributes to the recovery of function after local infarcts.

Learning a motor skill can also induce reorganization. Randy Nudo and colleagues trained monkeys to use precise movements of the thumb, index finger, and wrist to extract treats from a small well. After a monkey had become adept at the task, the area of its motor map in which intracortical microstimulation could evoke the skilled movements was larger than before training (Figure 37–16). If the monkey did not practice the task for a lengthy period, its skill level decreased, as did the cortical area from which the relevant movements could be elicited. Similar modifications of the representation of practiced actions have also been demonstrated in human motor cortex by functional imaging and transcranial magnetic stimulation.

John Donoghue and colleagues demonstrated that these adaptive changes depend on horizontal connections and local inhibitory circuits. They found two adjacent sites in the rat's motor map at which intracortical microstimulation caused contractions of muscles in the upper lips or forearm (Figure 37–17A). Within minutes after transection of the facial nerve innervating the lip muscles, stimulation of the lip-muscle site began to evoke contractions of forearm muscles.

In a related experiment they injected bicuculline into a forearm-muscle site in the motor cortex of an intact rat without a facial nerve transection to block the neurotransmitter GABA (γ-aminobutyric acid). Within minutes stimulation of the lip-muscle site evoked contractions of both lip and forearm muscles. They concluded that stimulation of the lip-muscle site activated local horizontal axons that projected into the forearm-muscle site, activity that was normally suppressed by GABAergic inhibitory interneurons (Figure 37–17B).

The Motor Cortex Contributes to Motor Skill Learning

One of the most remarkable properties of the brain is the adaptability of its circuitry to changes in the environment—the capacity to learn from experience and store the acquired knowledge as memories. When human subjects practice a motor skill their performance improves. Important advances have been made in understanding the mechanisms underlying the learning of motor skills, also known as procedural learning (see Chapter 66). For instance, Donoghue and colleagues found an increase in the synaptic strength of local horizontal connections between different parts of the arm motor map in rats that became increasingly skilled at reaching through a small hole in a transparent barrier to grasp, retrieve, and eat small food pellets.

Adaptation to perturbations of movement caused by external forces has been studied extensively in human subjects. One type of force field pushes on the arm in a direction perpendicular to the direction of the arm's movement; the strength of this force increases with movement speed. Although such viscous curl fields may seem odd, they are exactly the kind of forces that act on an arm when a person reaches out while simultaneously turning his or her body. Normally, these coriolis forces do not deflect the arm movement from its intended path because your motor system has learned to predict that these forces will arise during this natural behavior and generates a motor command that corrects for them in advance.

However, when a subject is stationary and unexpectedly encounters an experimentally generated viscous curl field for the first time during an arm movement, the arm is deflected sideways from its usual, nearly straight path and the hand path becomes curved. When the subject makes repeated movements in the same field, the movement paths become incrementally straighter until they are indistinguishable from movements without the curl field. If the force field is then unexpectedly turned off, the path of movement curves strongly in the opposite direction (Figure 37–18A). This after-effect demonstrates that the subject has changed the motor command required to produce the desired straight movement in anticipation of the perturbing effect of the force field.

As a subject adapts to the force field, motor behavior changes from feedback correction for actual perturbations to predictive feed-forward compensation for expected perturbation. Motor-learning theory suggests that this adaptive process may involve at least two distinct learning mechanisms, known as feedback-error learning and supervised learning.

In feedback-error learning sensory signals about the experienced error both guide the correction for the immediate perturbation and alter adaptive feedback control circuits to permit more efficient compensation for expected perturbation. In supervised learning the motor system gradually adapts internal models, neural circuits that learn the relationship between desired movements and required motor commands in that environment (see Chapter 33). An internal forward model estimates the state of the limb in the near future based on an efference copy of the motor command and sensory feedback of the ongoing movement, and uses this estimate to generate an error signal proportional to the deviation of the estimated movement from its desired kinematics. An internal inverse model uses this and other error signals to learn how to generate the motor command that will produce a desired movement by compensating in a predictive manner for the anticipated perturbation. Neural circuits that constitute these internal forward and inverse models are thought to be located in several brain structures, including the cerebellum, superior parietal cortex, premotor cortex, and primary motor cortex.

Emilio Bizzi and colleagues recorded the activity of the same primary motor cortex neurons over several hours in monkeys as the animals first made arm movements without an external force field, then while they made many movements to adapt to a viscous curl field, and finally while they readapted to the baseline condition (the "washout" period). As the monkeys adapted to the force field the directional tuning of many neurons gradually changed by 15 to 20 degrees from what it was before exposure to the viscous curl field, and then rotated back to the baseline during the washout period (Figure 37–18B). Arm muscles showed similar changes during adaptation and washout, implicating those neurons in the incremental adaptation of the motor command to the external curl field. Other neurons did not change directionality during either adaptation or washout, as if their signals communicated the desired movement kinematics across all force-field conditions.

Two other groups of neurons showed special properties. The directional tuning of one group changed when the monkeys switched from the null field to the curl field but did not return to baseline during washout (Figure 37–18B). The other group did not change during the original adaptation from null field to curl field but changed during washout. Bizzi proposed that these two groups of neurons retain the memory of one or the other of the successive learning episodes—adaptation and washout—in the task. That is, even though the motor performance of the monkeys returned to baseline, the functional state of the primary motor cortex did not revert to its original condition—a trace of the recent learning history persisted in the altered tuning properties of some neurons.

These and similar findings from other studies suggest that the motor map of the primary motor cortex is not static. Instead, the neuronal circuitry creates a dynamic, adaptive map that generates the motor commands required to accomplish desired actions under different conditions. This strongly implicates the primary motor cortex in the acquisition, retention, and recall of procedural skills, but does not clarify whether it functions primarily as part of a feedback controller, as an inverse internal model for task dynamics, or both.

Furthermore, recent studies have found that adaptive changes in motor cortex activity lag the improvement in motor performance by several trials during adaptation. This suggests that learning-related adjustments to motor commands are initially made elsewhere, with the cerebellum as one strong candidate. The primary motor cortex may thus be more strongly involved in the slower processes of long-term retention and recall of motor skills rather than the initial phase of learning a new skill.

The discovery of a topographically organized map of motor outputs to different parts of the body within a limited area of the cerebral cortex provided the first compelling experimental evidence for the cortical localization of motor function. For many years thereafter the role of the motor cortex was relegated to that of a simple map of muscles and muscle activity patterns by which the rest of the cerebral cortex controlled spinal motor neurons. Terms such as "upper-motor-neuron disease" were common in the clinical literature of an earlier era, but this view of motor cortex function is simplistic and incorrect.

Although the motor cortex does play a critical role in the control of voluntary movements, its neurons do not function like spinal motor neurons whose sole role is to encode muscle activity patterns. Instead, the motor cortex contains a heterogeneous population of neurons that contribute to the several operations required to convert a plan of action into the motor commands that execute the plan. The novel evolutionary development in primates of a direct, monosynaptic projection onto spinal motor neurons enables the primary motor cortex to control movements of the hand and fingers in a uniquely skillful way. This feature has been critical in the acquisition of dexterous hand movements that only higher primates and especially humans possess.

The primary motor cortex is part of a distributed network of cortical motor areas, each with its own role in voluntary motor control. The primary motor cortex should be regarded as a dynamic computational map whose internal organization and spinal connections convert central signals about motor intentions and sensory feedback about the current state of the limb into motor output commands, rather than as a static map of specific muscles or movements of body parts. The motor cortex also provides a substrate for adaptive alterations during the acquisition of motor skills and the recovery of function after lesions.